Vaccine Against Neonatal Infections

Design of a vaccine to immunize neonates against GBS infections through a durable maternal immune response.

Abstract

The DEVANI project's objective is to design immunization strategies capable of inducing in women strong, durable protective immunity against Group B Streptococcus (GBS) with placental transfer to the fetus, a goal which if achieved would protect at-risk infants. The effort is critical because direct vaccination is incapable of preventing diseases that affect neonates in the first days of life. GBS is a primary cause of neonatal septicemia and meningitis, affecting nearly one in every thousand live births. Without intrapartum antimicrobial prophylaxis over 80% of cases of GBS occur in the first seven days after birth; the remaining 20% of disease occurs between 8-90 days after birth.

The idea that immunization of women is an effective strategy for delivery of protective antibodies to their babies is supported by several US studies. These have suggested that high titres of maternal antibody to GBS capsular polysaccharides (CPS) correlate with reduced risk of disease in neonates. Several laboratories have shown that immunization of female mice with GBS CPS conjugated to a carrier protein results in protection of their offspring against lethal challenge with the major disease-causing strains of GBS. Moreover, Novartis scientists have identified three proteins that also confer protection in this model. However, to translate this research into a viable vaccine, large population studies regarding neonatal morbidity and the status of maternal antibodies are necessary.

For these reasons, the DEVANI consortium — funded by EC in the frame of the FP7, and comprised of 10 beneficiaries, including Novartis Vaccines and research groups in Italy, Spain, Belgium, Czech Republic, Germany, UK, Bulgaria and Denmark — is collecting GBS strains from cases of neonatal disease from across Europe to understand the distribution of GBS types and to select the most appropriate ones for inclusion in a future vaccine. The DEVANI project is also monitoring the level of maternal antibodies of both healthy GBS carriers and GBS-infected children. The project includes studies in vitro and in vivo in mice to identify appropriate adjuvant and delivery systems capable of inducing strong, long-lasting protective response in the mothers.

Sera and strains have been collected by all the participating countries. Currently the strains are being typed and studied to determine the presence of specific antigens to be included in a future vaccine. In parallel, the level of maternal antibodies required for protection is being assessed. The project is scheduled to conclude at the end of July 2011.